Previous studies from this laboratory have shown that in vitro conditions can be established which lead to an augmentation of cell- mediated cytotoxicity. Sensitization of peripheral blood lymphoid cells on a monolayer of autochthonous or allogeneic tumor cells results in an increase in cytotoxic activity against target tumor cells of the same histologic type. Extension of these studies with an emphasis on the determination of the operative mechanisms is now proposed. Improvements of the culture techniques to provide an even more cytotoxic effector cell population will be examined. Subpopulations of the mononuclear cells will be separated by various means and the role of thymus-derived (T) lymphocytes, non-thymus derived (B) lymphocytes, and adherent cells determined. Lymphoid cells will be depleted of each of these populations in turn and tested for the ability to be sensitized in vitro. Following sensitization, each population will be tested for effector cell activity. In addition to cytotoxicity, sensitized cells will be tested for proliferation and for tumor growth inhibition. The latter will be tested on human tumors grown in the cheek pouches of immunosuppressed hamsters. The effects of cancer patients' serum and of soluble antigens extracted from tumors on the sensitization and on effector cell activity will be measured. Attempts will be made to determine if the in vitro sensitization response to tumor antigens is a primary or secondary immune response.